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AIMS/HYPOTHESIS: Body niche-specific microbiota in maternal-neonatal dyads from gravidae with type 1 diabetes have not been quantitatively and functionally examined. Similarly, the impact of pregnancy-specific factors, such as the presence of comorbidities known to occur more frequently among gravidae with type 1 diabetes, including Caesarean delivery, as well as antibiotic prophylaxis, level of glycaemic control during each trimester of pregnancy and insulin administration, has not been adequately considered. The aims of this study were to characterise the maternal and neonatal microbiomes, assess aspects of microbiota transfer from the maternal microbiomes to the neonatal microbiome and explore the impact of type 1 diabetes and confounding factors on the microbiomes. METHODS: In this observational case-control study, we characterised microbiome community composition and function using 16S rRNA amplicon sequencing in a total of 514 vaginal, rectal and ear-skin swabs and stool samples derived from 92 maternal-neonatal dyads (including 50 gravidae with type 1 diabetes) and in-depth clinical metadata from throughout pregnancy and delivery. RESULTS: Type 1 diabetes-specific microbiota were identified among gravidae with type 1 diabetes and their neonates. Neonatal microbiome profiles of ear-skin swabs and stool samples were established, indicating the taxa more prevalent among neonates born to mothers with type 1 diabetes compared with neonates born to control mothers. Without taking into account the type 1 diabetes status of mothers, both delivery mode and intrapartum antibiotic prophylaxis were found to have an influence on neonatal microbiota composition (both p=0.001). In the logistic regression analysis involving all confounding variables, neonatal ear-skin microbiome variation was explained by maternal type 1 diabetes status (p=0.020) and small for gestational age birthweight (p=0.050). Moreover, in women with type 1 diabetes, a relationship was found between HbA1c levels >55 mmol/mol (>7.2%) measured in the first trimester of pregnancy and neonatal ear-skin microbiota composition (p=0.008). In the PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) assessment, pathways concerning carbohydrate biosynthesis were predicted as key elements of the microbial functional profiles dysregulated in type 1 diabetes. Additionally, in SourceTracker analysis, we found that, on average, 81.0% of neonatal microbiota was attributed to maternal sources. An increase in the contribution of maternal rectum microbiota and decrease in the contribution of maternal cervix microbiota were found in ear-skin samples of vaginally delivered neonates of mothers with type 1 diabetes compared with neonates born to control mothers (83.2% vs 59.5% and 0.7% vs 5.2%, respectively). CONCLUSIONS/INTERPRETATION: These findings indicate that, in addition to maternal type 1 diabetes, glycaemic dysregulation before/in the first trimester of pregnancy, mode of delivery and intrapartum antibiotic prophylaxis may contribute to the inoculation and formation of the neonatal microbiomes. DATA AVAILABILITY: The BioProject (PRJNA961636) and associated SRA metadata are available at http://www.ncbi.nlm.nih.gov/bioproject/961636 . Processed data on probiotic supplementation and the PICRUSt analysis are available in the Mendeley Data Repository ( https://doi.org/10.17632/g68rwnnrfk.1 ).
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Diabetes Mellitus Tipo 1 , Microbiota , Recién Nacido , Embarazo , Humanos , Femenino , ARN Ribosómico 16S/genética , Estudios de Casos y Controles , Filogenia , Microbiota/genéticaRESUMEN
Genetic factors underlying coronary artery disease (CAD) have been widely studied using genome-wide association studies (GWASs). However, the functional understanding of the CAD loci has been limited by the fact that a majority of GWAS variants are located within non-coding regions with no functional role. High cholesterol and dysregulation of the liver metabolism such as non-alcoholic fatty liver disease confer an increased risk of CAD. Here, we studied the function of non-coding single-nucleotide polymorphisms in CAD GWAS loci located within liver-specific enhancer elements by identifying their potential target genes using liver cis-eQTL analysis and promoter Capture Hi-C in HepG2 cells. Altogether, 734 target genes were identified of which 121 exhibited correlations to liver-related traits. To identify potentially causal regulatory SNPs, the allele-specific enhancer activity was analyzed by (1) sequence-based computational predictions, (2) quantification of allele-specific transcription factor binding, and (3) STARR-seq massively parallel reporter assay. Altogether, our analysis identified 1,277 unique SNPs that display allele-specific regulatory activity. Among these, susceptibility enhancers near important cholesterol homeostasis genes (APOB, APOC1, APOE, and LIPA) were identified, suggesting that altered gene regulatory activity could represent another way by which genetic variation regulates serum lipoprotein levels. Using CRISPR-based perturbation, we demonstrate how the deletion/activation of a single enhancer leads to changes in the expression of many target genes located in a shared chromatin interaction domain. Our integrative genomics approach represents a comprehensive effort in identifying putative causal regulatory regions and target genes that could predispose to clinical manifestation of CAD by affecting liver function.
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Enfermedad de la Arteria Coronaria/genética , Elementos de Facilitación Genéticos/genética , Predisposición Genética a la Enfermedad , Sitios de Carácter Cuantitativo/genética , Alelos , Cromatina/genética , Enfermedad de la Arteria Coronaria/patología , Femenino , Estudio de Asociación del Genoma Completo/métodos , Genómica , Humanos , Hígado/metabolismo , Masculino , Anotación de Secuencia Molecular , Especificidad de Órganos/genética , Polimorfismo de Nucleótido Simple/genética , Regiones Promotoras Genéticas/genética , Unión Proteica/genética , Factores de RiesgoRESUMEN
BACKGROUND: Obesity is a worldwide epidemic characterized by adipose tissue (AT) inflammation. AT is also a source of extracellular vesicles (EVs) that have recently been implicated in disorders related to metabolic syndrome. However, our understanding of mechanistic aspect of obesity's impact on EV secretion from human AT remains limited. METHODS: We investigated EVs from human Simpson Golabi Behmel Syndrome (SGBS) adipocytes, and from AT as well as plasma of subjects undergoing bariatric surgery. SGBS cells were treated with TNFα, palmitic acid, and eicosapentaenoic acid. Various analyses, including nanoparticle tracking analysis, electron microscopy, high-resolution confocal microscopy, and gas chromatography-mass spectrometry, were utilized to study EVs. Plasma EVs were analyzed with imaging flow cytometry. RESULTS: EVs from mature SGBS cells differed significantly in size and quantity compared to preadipocytes, disagreeing with previous findings in mouse adipocytes and indicating that adipogenesis promotes EV secretion in human adipocytes. Inflammatory stimuli also induced EV secretion, and altered EV fatty acid (FA) profiles more than those of cells, suggesting the role of EVs as rapid responders to metabolic shifts. Visceral AT (VAT) exhibited higher EV secretion compared to subcutaneous AT (SAT), with VAT EV counts positively correlating with plasma triacylglycerol (TAG) levels. Notably, the plasma EVs of subjects with obesity contained a higher number of adiponectin-positive EVs than those of lean subjects, further demonstrating higher AT EV secretion in obesity. Moreover, plasma EV counts of people with obesity positively correlated with body mass index and TNF expression in SAT, connecting increased EV secretion with AT expansion and inflammation. Finally, EVs from SGBS adipocytes and AT contained TAGs, and EV secretion increased despite signs of less active lipolytic pathways, indicating that AT EVs could be involved in the mobilization of excess lipids into circulation. CONCLUSIONS: We are the first to provide detailed FA profiles of human AT EVs. We report that AT EV secretion increases in human obesity, implicating their role in TAG transport and association with adverse metabolic parameters, thereby emphasizing their role in metabolic disorders. These findings promote our understanding of the roles that EVs play in human AT biology and metabolic disorders.
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Adipocitos , Tejido Adiposo , Vesículas Extracelulares , Inflamación , Obesidad , Humanos , Vesículas Extracelulares/metabolismo , Obesidad/metabolismo , Obesidad/patología , Adipocitos/metabolismo , Inflamación/patología , Inflamación/metabolismo , Tejido Adiposo/metabolismo , Tejido Adiposo/patología , Metabolismo de los Lípidos , Femenino , Masculino , Adulto , Ácidos Grasos/metabolismoRESUMEN
PURPOSE: The Scored Patient-Generated Subjective Global Assessment (PG-SGA©) is a validated nutritional screening, assessment, triage, and monitoring tool. The aim of this study was to perform translation, cultural adaptation, linguistic, and content validation of the translated and culturally adapted version of the PG-SGA for the Polish setting. METHODS: The study was performed in concordance with the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Principles. Patients (n = 174) and healthcare professionals (HCPs, n = 188) participated in the study. Comprehensibility and difficulty were assessed by patients for the PG-SGA Short Form, and by HCPs for the professional component. Content validity was assessed for the full PG-SGA by HCPs only. Evaluations were operationalized by a 4-point scale. Item and scale indices were calculated using the average item ratings divided by the number of respondents. Item indices < 0.78 required further analysis of the item, while scale indices ≥ 0.90 were defined as excellent and 0.80-0.89 as acceptable. RESULTS: The PG-SGA Short Form was rated as excellent for content validity (Scale-CVI = 0.90) by HCPs and easy to comprehend (Scale-CI = 0.96) and use (Scale-DI = 0.94) by patients. The professional component of the PG-SGA was perceived as acceptable for content validity (Scale-CVI = 0.80), comprehension (Scale-CI = 0.87), and difficulty (Scale-DI = 0.80). The physical exam was rated the least comprehensible and the most difficult, and with the lowest content validity. We found significant differences in scale indices (p < 0.05 for all) between HCPs with different professions and between those being familiar with PG-SGA and not. CONCLUSION: Translation and cultural adaptation of the PG-SGA for the Polish setting preserved the purpose and conceptual meaning of the original PG-SGA. Validation revealed that the Polish version of PG-SGA is well understood and easy to complete by patients and professionals, and is considered relevant by professionals. However, detailed results indicate the need for appropriate training of the Polish HCPs, especially physicians and nurses, mainly in the worksheets related to the metabolic demand and physical exam.
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Traducciones , Humanos , Femenino , Masculino , Polonia , Persona de Mediana Edad , Adulto , Reproducibilidad de los Resultados , Anciano , Evaluación Nutricional , Encuestas y Cuestionarios/normas , Personal de Salud/psicología , Adulto Joven , Psicometría/métodosRESUMEN
OBJECTIVE: The objective of this study is to explore and enhance the diagnostic process of unipolar and bipolar disorders. The primary focus is on leveraging automated processes to improve the accuracy and accessibility of diagnosis. The study aims to introduce an audio corpus collected from patients diagnosed with these disorders, annotated using the Clinical Global Impressions Scale (CGI) by psychiatrists. METHODS AND PROCEDURES: Traditional diagnostic methods rely on the clinician's expertise and consideration of co-existing mental disorders. However, this study proposes the implementation of automated processes in the diagnosis, providing quantitative measures and enabling prolonged observation of patients. The paper introduces a speech signal pipeline for CGI state classification, with a specific focus on selecting the most discriminative features. Acoustic features such as prosodies, MFCC, and LPC coefficients are examined in the study. The classification process utilizes common machine learning methods. RESULTS: The results of the study indicate promising outcomes for the automated diagnosis of bipolar and unipolar disorders using the proposed speech signal pipeline. The audio corpus annotated with CGI by psychiatrists achieved a classification accuracy of 95% for the two-class classification. For the four- and seven-class classifications, the results were 77.3% and 73%, respectively, demonstrating the potential of the developed method in distinguishing different states of the disorders.
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Trastorno Bipolar , Humanos , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/fisiopatología , Femenino , Masculino , Habla/fisiología , Adulto , Aprendizaje Automático , Procesamiento de Señales Asistido por Computador , Persona de Mediana Edad , Diagnóstico DiferencialRESUMEN
Radiological procedures utilising intravascular contrast media (ICM) are fundamental to modern medicine, enhancing diagnostics and treatment in diverse medical fields. However, the application of ICM has been constrained in patients with compromised kidney function due to perceived nephrotoxic risks, called contrast-induced nephropathy or contrastinduced acute kidney injury. Historical evidence marked ICM as a possible contributor to kidney damage. This led to restrictive guidelines advocating limited ICM use in patients with impaired renal function, preventing crucial radiographic interventions in patients with acute kidney injury (AKI) and chronic kidney disease. Recent advances challenge these traditional views. In particular, no direct causal relationship has been confirmed between contrast admi-nistration and elevated serum creatinine concentrations in humans. Furthermore, contemporary research models and meta-analyses do not associate AKI with contrast usage. This paper, prepared by a cross-disciplinary team of nephrologists and radiologists, presents updated guidelines for ICM application amid renal function impairments, emphasising the reduced nephrotoxic risks currently understood and loosening the previous restrictive approach in patients with renal dysfunction.
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The need for objective data-driven usability testing of VR applications is becoming more tangible with the rapid development of numerous VR applications and their increased accessibility. Traditional methods of testing are too time and resource consuming and might provide results that are highly subjective. Thus, the aim of this article is to explore the possibility of automation of usability testing of VR applications by using objective features such as HMD built-in head and hands tracking, EEG sensor, video recording, and other measurable parameters in addition to automated analysis of subjective data provided in questionnaires. For this purpose, a simple VR application was created which comprised relatively easy tasks that did not generate stress for the users. Fourteen volunteers took part in the study and their signals were monitored to acquire objective automated data. At the same time the observer was taking notes of subjects' behaviour, and their subjective opinions about the experience were recorded in a post-experiment questionnaire. The results acquired from signal monitoring and questionnaires were juxtaposed with observation and post-interview results to confirm the validity and efficacy of automated usability testing. The results were very promising, proving that automated usability testing of VR applications is potentially achievable.
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Interfaz Usuario-Computador , Realidad Virtual , Automatización , Humanos , Proyectos Piloto , Diseño Centrado en el UsuarioRESUMEN
Virtual reality (VR) is a well-established technology in medicine. Head-mounted displays (HMDs) have made VR more accessible in many branches of medical research. However, its application in balance evaluation has been vague, and comprehensive literature on possible applications of VR in posture measurement is scarce. The aim of this review is to conduct a literature search on the application of immersive VR delivered using a head-mounted display in posturographic measurements. A systematic search of two databases, PubMed and Scopus, using the keywords "virtual reality" and "posturography," was performed following PRISMA guidelines for systematic reviews. Initial search results returned 89 non-duplicate records. Two reviewers independently screened the abstracts. Sixteen papers fulfilled the inclusion criteria and none of the exclusion criteria and were selected for complete text retrieval. An additional 16 records were identified from citation searching. Ultimately, 21 studies were included in this review. virtual reality is often used as additional visual stimuli in static and dynamic posturography evaluation. Only one study has attempted to evaluate a VR environment in a head-mounted display as an independent method in the assessment of posture. Further research should be conducted to assess HMD VR as a standalone posturography replacement.
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Gafas Inteligentes , Realidad Virtual , PosturaRESUMEN
BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) has been associated with multiple metabolic abnormalities. By applying a non-targeted metabolomics approach, we aimed at investigating whether serum metabolite profile that associates with NAFLD would differ in its association with NAFLD-related metabolic risk factors. METHODS & RESULTS: A total of 233 subjects (mean ± SD: 48.3 ± 9.3 years old; BMI: 43.1 ± 5.4 kg/m2 ; 64 male) undergoing bariatric surgery were studied. Of these participants, 164 with liver histology could be classified as normal liver (n = 79), simple steatosis (SS, n = 40) or non-alcoholic steatohepatitis (NASH, n = 45). Among the identified fasting serum metabolites with higher levels in those with NASH when compared to those with normal phenotype were the aromatic amino acids (AAAs: tryptophan, tyrosine and phenylalanine), the branched-chain amino acids (BCAAs: leucine and isoleucine), a phosphatidylcholine (PC(16:0/16:1)) and uridine (all FDRp < 0.05). Only tryptophan was significantly higher in those with NASH compared to those with SS (FDRp < 0.05). Only the AAAs tryptophan and tyrosine correlated positively with serum total and LDL cholesterol (FDRp < 0.1), and accordingly, with liver LDLR at mRNA expression level. In addition, tryptophan was the single AA associated with liver DNA methylation of CpG sites known to be differentially methylated in those with NASH. CONCLUSIONS: We found that serum levels of the NASH-related AAAs and BCAAs demonstrate divergent associations with serum lipids. The specific correlation of tryptophan with LDL-c may result from the molecular events affecting LDLR mRNA expression and NASH-associated methylation of genes in the liver.
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Cirugía Bariátrica , Enfermedad del Hígado Graso no Alcohólico , Adulto , Aminoácidos de Cadena Ramificada , Humanos , Masculino , Persona de Mediana Edad , FosfatidilcolinasRESUMEN
The proteasome to immunoproteasome (iPS) switch consists of ß1, ß2 and ß5 subunit replacement by low molecular weight protein 2 (LMP2), LMP7 and multicatalytic endopeptidase-like complex-1 (MECL1) subunits, resulting in a more efficient peptide preparation for major histocompatibility complex 1 (MHC-I) presentation. It is activated by toll-like receptor (TLR) agonists and interferons and may also be influenced by genetic variation. In a previous study we found an iPS upregulation in peripheral cells of patients with immunoglobulin A nephropathy (IgAN). We aimed to investigate in 157 IgAN patients enrolled through the multinational Validation Study of the Oxford Classification of IgAN (VALIGA) study the relationships between iPS switch and estimated glomerular filtration rate (eGFR) modifications from renal biopsy to sampling. Patients had a previous long follow-up (6.4 years in median) that allowed an accurate calculation of their slope of renal function decline. We also evaluated the effects of the PSMB8/PSMB9 locus (rs9357155) associated with IgAN in genome-wide association studies and the expression of messenger RNAs (mRNAs) encoding for TLRs and CD46, a C3 convertase inhibitor, acting also on T-regulatory cell promotion, found to have reduced expression in progressive IgAN. We detected an upregulation of LMP7/ß5 and LMP2/ß1 switches. We observed no genetic effect of rs9357155. TLR4 and TLR2 mRNAs were found to be significantly associated with iPS switches, particularly TLR4 and LMP7/ß5 (P < 0.0001). The LMP7/ß5 switch was significantly associated with the rate of eGFR loss (P = 0.026), but not with eGFR at biopsy. Fast progressors (defined as the loss of eGFR >75th centile, i.e. -1.91 mL/min/1.73 m2/year) were characterized by significantly elevated LMP7/ß5 mRNA (P = 0.04) and low CD46 mRNA expression (P < 0.01). A multivariate logistic regression model, categorizing patients by different levels of kidney disease progression, showed a high prediction value for the combination of high LMP7/ß5 and low CD46 expression.
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Glomerulonefritis por IGA , Complejo de la Endopetidasa Proteasomal , Estudio de Asociación del Genoma Completo , Glomerulonefritis por IGA/genética , Humanos , Proteína Cofactora de Membrana , Complejo de la Endopetidasa Proteasomal/genética , Complejo de la Endopetidasa Proteasomal/metabolismo , ARN Mensajero , Regulación hacia ArribaRESUMEN
BACKGROUND: Arteriovenous fistulae (AVFs) may remain patent after kidney transplantation (KTx), contributing to maladaptive cardiac remodeling. The flow in AVFs is associated with the diameter of its vessels and thus with the AVF location. The main objective of this study is to assess the influence of AVF location and its patency on the self-reported quality of life (QOL) of kidney transplant recipients (KTRs) with past history of hemodialysis. METHODS: To gain clinical data, during a scheduled visit, 353 KTRs were asked to fill out an anonymous questionnaire. From this group, 284 respondents were found eligible for analysis. The outcome was defined as prevalence of symptoms and health status, measured with the Left Ventricular Dysfunction-36 (LVD-36) Questionnaire in symptomatic patients. RESULTS: The hemodialysis patients (n = 243) were divided into two groups according to AVF location, i.e., DAVF - distally located AVF - (n = 174) and PAVF - proximally located AVF - (n = 69). The proportion of patients with heart failure (HF) was higher in PAVF group (24% vs. 12%, p = 0.0482). In the multivariable regression, PAVF, serum creatinine levels, and the presence of HF or coronary artery disease (CAD) remained independent predictors of lower functional capacity. Among patients with heart disease, the presence of active AVF was independently associated with worse functional outcome (higher LVD-36 scores). CONCLUSIONS: The influence of persistent PAVF in KTRs seems to be unfavorable, especially when coexisting with CAD or HF. Abbreviations: AVF arteriovenous fistula; BMI body mass index; CAD coronary artery disease; D-AVF distally-located arteriovenous fistula; EC exercise capacity; HD hemodialysis; HF heart failure; KTx kidney transplantation; KTR kidney transplant recipient; LVD-36 Left Ventricle Disfunction - 36; LVEF left ventricle ejection fraction; LVH left ventricle hypertrophy; NYHA New York Heart Association; P-AVF proximally located arteriovenous fistula; PD peritoneal dialysis; PRO patient-reported outcomes; QOL quality of life.
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Fístula Arteriovenosa/patología , Derivación Arteriovenosa Quirúrgica/métodos , Insuficiencia Cardíaca/complicaciones , Hipertrofia Ventricular Izquierda/complicaciones , Trasplante de Riñón/efectos adversos , Adulto , Anciano , Fístula Arteriovenosa/etiología , Estudios Transversales , Femenino , Insuficiencia Cardíaca/fisiopatología , Humanos , Hipertrofia Ventricular Izquierda/fisiopatología , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Calidad de Vida , Diálisis Renal , Volumen Sistólico , Receptores de Trasplantes , Grado de Desobstrucción Vascular , Función Ventricular IzquierdaRESUMEN
Bee products have been known for centuries for their versatile healing properties. In recent decades they have become the subject of documented scientific research. This review aims to present and compare the impact of bee products and their components as antimicrobial agents. Honey, propolis, royal jelly and bee venom are bee products that have antibacterial properties. Sensitivity of bacteria to these products varies considerably between products and varieties of the same product depending on their origin. According to the type of bee product, different degrees of activity were observed against Gram-positive and Gram-negative bacteria, yeasts, molds and dermatophytes, as well as biofilm-forming microorganisms. Pseudomonas aeruginosa turned out to be the most resistant to bee products. An analysis of average minimum inhibitory concentration values for bee products showed that bee venom has the strongest bacterial effectiveness, while royal jelly showed the weakest antibacterial activity. The most challenging problems associated with using bee products for medical purposes are dosage and safety. The complexity and variability in composition of these products raise the need for their standardization before safe and predictable clinical uses can be achieved.
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Antibacterianos , Venenos de Abeja , Abejas/química , Ácidos Grasos , Miel , Própolis , Animales , Antibacterianos/química , Antibacterianos/uso terapéutico , Venenos de Abeja/química , Venenos de Abeja/uso terapéutico , Ácidos Grasos/química , Ácidos Grasos/uso terapéutico , Bacterias Gramnegativas/crecimiento & desarrollo , Bacterias Grampositivas/crecimiento & desarrollo , Própolis/química , Própolis/uso terapéuticoRESUMEN
Post-transplant lymphoproliferative disorder (PTLD) is serious life-threating complication of transplantation. The clinical picture differs from lymphomas observed in the general population, with different manifestation, histopathology, higher aggressiveness with involvement of sites beyond the primary lymph node, and poorer outcome. The objective of the study was to present nine cases of PTLD observed in our centre among the kidney transplant recipient population and discuss the results with up-to-date literature. We performed a retrospective single-centre assessment of PTLD incidence in the cohorts of kidney transplant recipients followed by our centre. We found nine cases of PTLD, five men and four woman, aged from 26 to 67 years at the time of diagnosis (mean [SD] 48 [5] years), transplanted between 1997 and 2013. The disease was diagnosed between 2002 and 2017, from 6 to 440 months after transplantation (mean [SD] 96 [137] months). A diffuse large B-cell lymphoma was found in seven cases early as well as late after transplantation, and two patients presented T-cell lymphoma. Five patients achieved complete remission with no relapses after 6 to 13 months of treatment. In three cases the remission was achieved by switching to mammalian target of rapamycin inhibitors (mTORi) only. Four recipients died from 2 weeks to 15 months after PTLD was diagnosed. Although the diagnostic criteria of different forms of PTLD are commonly known, rapid and correct diagnosis is not easy. PTLD is a relatively a rare disease, so there are too few studies and little consensus on the optimal treatment.
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BACKGROUND & AIMS: Alterations in liver phosphatidylcholine (PC) metabolism have been implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Although genetic variation in the phosphatidylethanolamine N-methyltransferase (PEMT) enzyme synthesizing PC has been associated with disease, the functional mechanism linking PC metabolism to the pathogenesis of non-alcoholic steatohepatitis (NASH) remains unclear. METHODS: Serum PC levels and liver PC contents were measured using proton nuclear magnetic resonance (NMR) spectroscopy in 169 obese individuals [age 46.6 ± 10 (mean ± SD) years, BMI 43.3 ± 6 kg/m2 , 53 men and 116 women] with histological assessment of NAFLD; 106 of these had a distinct liver phenotype. All subjects were genotyped for PEMT rs7946 and liver mRNA expression of PEMT and glycine N-methyltransferase (GNMT) was analysed. RESULTS: Liver PC content was lower in those with NASH (P = 1.8 x 10-6 ) while serum PC levels did not differ between individuals with NASH and normal liver (P = 0.591). Interestingly, serum and liver PC did not correlate (rs = -0.047, P = 0.557). Serum PC and serum cholesterol levels correlated strongly (rs = 0.866, P = 7.1 x 10-49 ), while liver PC content did not correlate with serum cholesterol (rs = 0.065, P = 0.413). Neither PEMT V175M genotype nor PEMT expression explained the association between liver PC content and NASH. Instead, liver GNMT mRNA expression was decreased in those with NASH (P = 3.8 x 10-4 ) and correlated with liver PC content (rs = 0.265, P = 0.001). CONCLUSIONS: Decreased liver PC content in individuals with the NASH is independent of PEMT V175M genotype and could be partly linked to decreased GNMT expression.
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Glicina N-Metiltransferasa/genética , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/patología , Fosfatidilcolinas/análisis , Fosfatidiletanolamina N-Metiltransferasa/genética , Adulto , Animales , Femenino , Humanos , Hígado/patología , Masculino , Persona de Mediana Edad , Obesidad/patología , Espectroscopía de Protones por Resonancia Magnética , ARN MensajeroRESUMEN
BACKGROUND: Complement is thought to play a role in immunoglobulin A nephropathy (IgAN), though the activating mechanisms are unknown. This study focused on the gene expression of CD46 and CD55, two key molecules for regulating C3 convertase activity of lectin and alternative complement pathways at a cellular level. METHODS: The transcriptional expression in peripheral white blood cells (WBCs) of CD46 and CD55 was investigated in 157 patients enrolled by the Validation of the Oxford Classification of IgAN group, looking for correlations with clinical and pathology features and estimated glomerular filtration rate (eGFR) modifications from renal biopsy to sampling. Patients had a previous median follow-up of 6.4 (interquartile range 2.8-10.7) years and were divided into progressors and non-progressors according to the median value of their velocity of loss of renal function per year (-0.41 mL/min/1.73 m2/year). RESULTS: CD46 and CD55 messenger RNA (mRNA) expression in WBCs was not correlated with eGFR values or proteinuria at sampling. CD46 mRNA was significantly correlated with eGFR decline rate as a continuous outcome variable (P = 0.014). A significant difference was found in CD46 gene expression between progressors and non-progressors (P = 0.013). CD46 and CD55 mRNA levels were significantly correlated (P < 0.01), although no difference between progressors and non-progressors was found for CD55 mRNA values. The prediction of progression was increased when CD46 and CD55 mRNA expressions were added to clinical data at renal biopsy (eGFR, proteinuria and mean arterial blood pressure) and Oxford MEST-C (mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis, presence of any crescents) score. CONCLUSIONS: Patients with progressive IgAN showed lower expression of mRNA encoding for the complement inhibitory protein CD46, which may implicate a defective regulation of C3 convertase with uncontrolled complement activation.
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Biomarcadores/sangre , Inactivadores del Complemento/sangre , Glomerulonefritis por IGA/diagnóstico , Proteína Cofactora de Membrana/sangre , Adulto , Progresión de la Enfermedad , Femenino , Regulación de la Expresión Génica , Glomerulonefritis por IGA/sangre , Glomerulonefritis por IGA/genética , Humanos , Masculino , Proteína Cofactora de Membrana/genética , Persona de Mediana Edad , Pronóstico , ARN Mensajero/sangre , ARN Mensajero/genéticaRESUMEN
Aims: Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) are members of the glycosylphosphatidylinositol (GPI)-linked immunoglobulin (Ig) superfamily and take part in regulation of cell adhesion, tumor suppression and angiogenesis. Overexpression of CEACAM 1, 5 and 6 is widely described in several gastrointestinal epithelial tumors. The aim of study was to evaluate the expression of CEACAM 1, CEACAM 5 and CEACAM 6 in the most common precursor lesions of pancreatic ductal adenocarcinoma -pancreatic intraepithelial neoplasia (PanIN). Methods and results: The study group consisted of 32 patients treated for chronic pancreatitis and 38 patients with pancreatic ductal adenocarcinoma who also had pancreatic intraepithelial neoplasia. The expression of CEACAM was performed by immunohistochemical method and evaluated using 3-point scale: 0 - lack of positive reaction in pancreatic intraepithelial neoplasia, 1 (weak and moderate) - reaction present in 1-30% epithelial cells in PanIN and 2 (strong) - reaction present in >30% epithelial cells in PanIN. Expression of CEACAM 1, 5 and 6 increased with increasing degree of advancement of PanIN. Differences in expression of CEACAM 1, 5 and 6 between normal pancreatic ducts and different degrees of PanIN were statistically significant (p<0.001). We observed relationship between CEACAM1 expression and localization of PanIN in different parts of the pancreas. Conclusions: CEACAM 1, CEACAM 5 and CEACAM 6 expression appears to be an early event in pancreatic carcinogenesis. Moreover, expression of CEACAM 1, 5 and 6 may represent a useful biomarker that may aid in the identification of precancerous lesions in the pancreas.
Asunto(s)
Adenocarcinoma/genética , Antígenos CD/genética , Antígeno Carcinoembrionario/genética , Carcinoma Ductal Pancreático/genética , Moléculas de Adhesión Celular/genética , Adenocarcinoma/complicaciones , Adenocarcinoma/patología , Anciano , Biomarcadores de Tumor/genética , Carcinogénesis/genética , Carcinoma in Situ/complicaciones , Carcinoma in Situ/genética , Carcinoma in Situ/patología , Carcinoma Ductal Pancreático/patología , Femenino , Proteínas Ligadas a GPI/genética , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Masculino , Persona de Mediana Edad , Páncreas/metabolismo , Páncreas/patología , Pancreatitis Crónica/complicaciones , Pancreatitis Crónica/genética , Pancreatitis Crónica/patologíaRESUMEN
Automatic emotion recognition has become an important trend in many artificial intelligence (AI) based applications and has been widely explored in recent years. Most research in the area of automated emotion recognition is based on facial expressions or speech signals. Although the influence of the emotional state on body movements is undeniable, this source of expression is still underestimated in automatic analysis. In this paper, we propose a novel method to recognise seven basic emotional states-namely, happy, sad, surprise, fear, anger, disgust and neutral-utilising body movement. We analyse motion capture data under seven basic emotional states recorded by professional actor/actresses using Microsoft Kinect v2 sensor. We propose a new representation of affective movements, based on sequences of body joints. The proposed algorithm creates a sequential model of affective movement based on low level features inferred from the spacial location and the orientation of joints within the tracked skeleton. In the experimental results, different deep neural networks were employed and compared to recognise the emotional state of the acquired motion sequences. The experimental results conducted in this work show the feasibility of automatic emotion recognition from sequences of body gestures, which can serve as an additional source of information in multimodal emotion recognition.
RESUMEN
Dietary supplements, particularly those containing ingredients of natural origin, may contain microbiological contaminants, both bacterial and fungal. The present study evaluated the microbiological purity of selected dietary supplements containing plant-based ingredients before their release to the market, as well as raw materials of plant origin which are used in the production of such supplements. A total of 122 samples of supplements and 30 materials of plant origin were studied, with 92.1% exhibiting different degrees of bacterial contamination. Eight samples (5.3%) were contaminated by aerobic bacteria in amounts exceeding 105 CFU/g. Five (3.3%) of the studied supplements were found to contain bacteria from the family Enterobacteriaceae at a level exceeding 103 CFU/g. Furthermore, a considerable proportion of the studied samples (86.8%) contained fungal contamination. Microbiological contamination may contribute to a deterioration in quality and stability of dietary supplements. In addition, high levels of pathogenic bacteria and microorganisms may pose a risk to consumers.